Thymic lymphocytic lymphoma develops in mice spontaneously and in this case it is apparently induced by endogenous viruses (MuLV) or it can be induced by skin painting with 3-methylcholanthrene (MCA). The factors possibly responsible for the disease induction either by the virus or the carcinogen are being investigated. Expression of endogenous MuLV: A high incidence of spontaneous lymphomas has been observed so far only in inbred strains (AKR and C58) which early in life already express a high level of endogenous MuLV. Consequently, strains which express low MuLV rarely develop the disease spontaneously but some (RF, DBA/2, DBA/1) respond to MCA painting with a high incidence of lymphomas. Whether this lymphomagenic effect might involve the carcinogen increasing the level of MuLV expression is being investigated by means of different techniques. The induction in mice of the enzyme system aryl hydrocarbon hydroxylase (AHH) by MCA: Whether or not MCA exerts this effect is governed by the Ah locus, and this in turn influences the neoplastic effects of the carcinogen. Thus, whereas a high rate of spontaneous lymphoma occurs in AHH inducible (C58) as well as in AHH noninducible (AKR) strains, MCA induces the disease only in AHH-noninducible strains. However, some of these strains are highly resistant to this lymphomagenic effect. This indicates that the AHH non-inducible phenotype only contributes conditions favorable for the lymphomas to develop in the MCA-painted mice but that the actual occurrence of the disease is governed by genes unrelated to the Ah locus. Studies are in progress to identify these genes and to determine whether they might influence the spontaneous development of the lymphomas.